Hcde 333 Presentation

7/27/2019 Hcde 333 Presentation

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Toxicology ReportEthinyl Estradiol

Abbi, Anh, Melody and Paul


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Purpose

Know the environmental sources of

ethinyl estradiol Understand the human health effects

connected to ethinyl estradiol


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Overview

1. About Ethinyl Estradiol (EE2)

2. Environmental Sources

3. Health Effects

4. Limitations

5. Conclusion

6. References


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1. About Ethinyl Estradiol (EE2)

Synthetic estrogen hormone

Used in birth control and for hormonal therapies

Birth control dose is usually 20-60 ug daily

Only 50% is absorbed on average in the human body


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1. Environmental Cycle of EE2


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2. Environmental Sources -Overview

Primarily water exposure

Can enter soil and air through water,but likelihood of human contact is slim

and amount would be small

Enters water through sewage

Has been detected at levels up to 273ng/L

Chance of meaningful, unintentionalcontact is minimal


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2.1 Route of Exposure

Oral, through unintentional ingestion

Via water


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2.1.2 How EE2 enters the watera. human sources

Consumed in birth control pills and other hormonaltherapieso Over 60 million women worldwide take birth

control pills

30-90% of compound is not absorbed by the bodyand is then excreted

Based on a 60% excretion rate, ~720kg ethinylestradiol enters the water supply annually


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2.1.2 How EE2 enters the waterb. animal sources

Currently, no known significant animal contributors

Other types of estrogens from animals may present

a concern, but not ethinyl estradiol

If ethinyl estradiol becomes a common compound forlarge-scale animal use, then animal sources would

become a significant contributor of ethinyl estradiolto concentrations in water


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2.1.2 How EE2 enters the waterc. industrial sources

No significant sources documented

However, increased concentrations of other

pharmaceuticals in water sources near productionfacilities have been found

More research is needed


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2.2 Amount of EE2 in water

In a survey of water sources: 0.1 ng/L (belowdetection limit) to 273 ng/L

In raw sewage, generally about 10 ng/Lo has been found in higher concentrations

Eventually biodegrades in water, but"pseudopersistent" in areas where sewage is

continually discharged


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2.3 Removal of EE2 from wastewater

Significant amounts of ethinyl estradiol can beremoved with wastewater treatment

Primary wastewater treatment can remove ~14% of

total estrogen hormones (ethinyl estradiol makes upa small portion of the total)

A type of secondary treatment called activatedsludge can eliminate over 60% of ethinyl estradiol

from wastewater


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2.4 Likelihood of human contactwith environmental EE2

In general, contact with significant amounts unlikely

Drinking water generally not the same source wherewastewater is released

Ethinyl estradiol eventually degrades in water, soassuming that the water will not be immediatelyconsumed, contact with the compound is unlikely

In closed water reuse systems, contact likelihoodincreases due to the reuse of wastewater as drinkingwater


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3. Health Effects Related to EE2

Pharmaceutical Source: Cardiovascular Respiratory Reproductive Death

Genotoxic Carcinogenic Neurological Behavorial

Environmental Source: Immunological Reproductive Developmental


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3.1 Health Effects - Systemic

Cardiovascular

Systemic Hypertension Myocardial Ischemia Myocardial Infarction

(Heart Attack) Thromboembolic Disease(Blood Clot)

Fluid Retention Edema

Respiratory

Pulmonary Hypertension Pulmonary Emboli

(Clot in lung arteries)


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3.2 Health Effects - Immunological

In mammals and fish estrogen including ethinyl estradiolinhibits different part of immune response

Animal studies show immunosupression via decreasinglymphocyte production, especially in male fish exposed

to contaminated effluent.

Studies also indicate that ethinyl estradiol is more potentin mixed concoctions than when administered alone.


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3.3 Health Effects - Reproductive

Oral Contraceptives:o breakthrough vaginal bleedingo glucose intoleranceo breast tenderness

Case Report: male employee of a pharmaceuticalcompany making contraceptive pills containingethinyl estradiol developing prolactin secretingadenoma

Environmental Exposure:oAnimal studies show decline in reproductive

successo Feminization in male fish

3 ff


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3.4 Health Effects - Developmental

Exposure of zebrafish to ethinyl estradiol at a concentration of14-16 ng/L developed ova-testis sex organs.

Relation to humans: Dose is environmentally relavent. Childrenthat grow up with both sex organs have developed genderidentity disorders, depression and dissatisfaction with their

assigned sex. Limitations to data: Fish are very different than humans. There

needs to be studies to correlate ethinyl estradiol exposure tointersex humans.

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3.5 Health Effects - Genotoxic

In the presence of metabolic activation system (S9 mix) withNADP, ethinyl estradiol was found to cause genotoxicdamage to human lymphocytes at 5 and 10 M.o A lymphocyte is a type of white blood cell.o NADP is an important molecule used in cellular respiration to

make energy.o The S9 mix is a mixture of several liver enzymes.

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3.6 Health Effects - Carcinogenic

Women receiving estrogen replacement therapy, includingethinyl estradiol, reported a 2 to 15 fold increase in the riskof endometrial cancer.o Endometrial cancer occurs in the lining of the uterus.

Estrogen replacement therapy uses estrogens to stop theeffects of menopause after the ovaries have been removed

or have stopped functioning.

Limitations to data: Estrogen replacement therapy uses ethinylestradiol as well as a variety of other estrogens. More research isneeded on only ethinyl estradiol for estrogen replacement

therapy.


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3.9 Health Effects - Death

No data found for human death but death can occurfrom secondary complications.

No death in animal studies using fish

Death in studies using rats and mices with an LD50 of2952 mg/kg in rats and 1737 mg/kg in mice

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4. Limitations of References &Existing Data

Not enough human studies dealing with environmentalexposure

Not even that many mammal studies...

Limited to primarily to discussion of sewage treatment,no real discussions of ambient concentrations indrinking water sources

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5. Conclusion

More research is needed about the health effectsrelated to ethinyl estradiol and the concentrationsfound in drinking water sources

More research is needed to address ethinyl estradiolas a single substance rather than estrogen mixed Current data does not suggest that ethinyl estradiol in

water presents a great threat to human health

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6. References

Andersen H, Siegrist H, Halling-Sorensen B, Ternes TA (2003) Fate of estrogensin a municipal sewage treatment plant. Environ Sci Technol 37:40214026.

Combalbert, S., & Hernandez-Raquet, G. (May 01, 2010). Occurrence, fate, andbiodegradation of estrogens in sewage and manure.Applied Microbiology andBiotechnology, 86, 6, 1671-1692.

Combined Estrogen-Progestogen Contraceptives and CombinedEstrogen-Progestogen Menopausal Therapy. IARC Monographs on theEvaluation of Carcinogenic Risks to Humans, 91. (2007)

Pub Chem. (n.d.). Substance Summary. In Ethinyl Estradiol. Retrieved February20, 2011, fromhttp://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=9737&viewopt =DepositedSiddique, Y.H, Beg, T, & Afzal,. (2010). Genotoxic potential of ethinylestradiol incultured mammalian cells. Chemico-Biological Interactions,151 (5), 133-141.Slone, D., Shapiro, S., Kaufman, D. W., Rosenberg, L., Miettinen, O. S., & Stolley,P. D. (January 01, 1981). Risk of myocardial infarction in relation to current and

discontinued use of oral contraceptives. The New England Journal of Medicine,305, 8, 420-4.Steinberg K.K. (1991) A meta-analysis of the effect of estrogen replacementtherapy on the risk of breast cancer. JAMA. 265:1985-1990.National Library of Medicine. (n.d.). Hazardous Substance Data Bank. InEthinylestradiol. Retrieved February 20, 2011, from http://toxnet.nlm.nih.gov/cgi-

bin/sis/search/r?dbs+hsdb:@term+@rn+@rel+57-63-6.
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=9737&viewopthttp://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=9737&viewopthttp://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@rn+@rel+57-63-6http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@rn+@rel+57-63-6http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@rn+@rel+57-63-6http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@rn+@rel+57-63-6http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@rn+@rel+57-63-6http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@rn+@rel+57-63-6http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@rn+@rel+57-63-6http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@rn+@rel+57-63-6http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@rn+@rel+57-63-6http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=9737&viewopthttp://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=9737&viewopt

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Hcde 333 Presentation